Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency

Chalmers, R. A.; Lawson, A. M.; Borud, O.

doi:10.1016/0009-8981(77)90018-3

Cited by 24 publications

(10 citation statements)

References 13 publications

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“…There have been few adequate reports on organic acids in patients with congenital lactic aeidoses other than those of Van Biervliet and his co-workers (Van Biervliet et al, 1977a,b;Willems, 1978) and ofthe author and his co-workers (Chalmers et al, 1977(Chalmers et al, , 1978, organic acid patterns in urine frequently being described as 'normal' (Baal et aI., 1981). In the present study, quantitative extraction methods have been used, based upon the use of DEAE Sephadex (see Chalmers and Lawson, 1982), combined with quantitative capillary gas chromatography on fused silica columns (Tracey et aI., 1983), and capillary gas chromatography-mass spectrometry.…”

Section: Cytochrome Deficienciesmentioning

confidence: 94%

“…Chalmers et al (1977) suggested from studies on a patient with pyruvate decarboxylase (E1) deficiency that the quantitative pattern oforganic acids in such patients, together with the clinical and biochemical profiles of the patients, would allow indication of the area of the underlying primary enzyme deficiency, thereby reducing and refining the otherwise considerable amount of investigative and often frustrating enzymology required to achieve a diagnosis (Robinson et aI., 1980).…”

Section: Cytochrome Deficienciesmentioning

confidence: 99%

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Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis

Chalmers

1984

J of Inher Metab Disea

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The differential diagnosis of patients with apparent congenital lactic acidoses poses one of the most intractable problems in the study of patients with disorders of organic acid metabolism. An outline of the factors leading to a lactic acidosis, particularly in infants and young children, together with a brief review of the known causes of congenital lactic acidosis, are presented. Quantitative examination of the organic acids excreted by patients with proven enzyme deficiencies causing congenital lactic acidosis has demonstrated the characteristic patterns that are associated with specific disorders of this kind. After exclusion of uninherited, acquired and secondary metabolic causes of lactic acidosis, the quantitative patterns of organic acid excretion, together with other clinical and biochemical observations, provide valuable indicators of the area of the underlying primary metabolic disorder for subsequent selected, confirmatory, enzymology. The study of organic acids has a key and central role in the approach to the clinical and biochemical investigation and diagnosis of patients with congenital lactic acidoses.

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Section: Cytochrome Deficienciesmentioning

confidence: 94%

Section: Cytochrome Deficienciesmentioning

confidence: 99%

Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis

Chalmers

1984

J of Inher Metab Disea

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“…(2) A patient with severe lactic acidosis and a near total deficiency of pyruvic acid decarboxylase [2].…”

Section: Clinical and Biochemical Delineationmentioning

confidence: 99%

A familial progressive neurodegenerative disease with 2-oxoglutaric aciduria

et al. 1982

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A boy and a girl born to a consanguineous Tunisian couple are suffering from a slowly progressive nervous disorder. Initially they both had normal psychomotor development with acquisition of gait and speech. First symptoms in the boy were athetoid movements during the second year of life. He later lost all motor and language skills and developed muscular rigidity and intention tremor. At the age of five years, he was completely bedridden while he appeared mentally much less affected. His younger sister followed a similar course. The major specific abnormality detected was a strikingly elevated excretion of 2-oxoglutaric acid, which was identified by gas liquid chromatography, mass spectrometry, and enzymatic analysis. 2-oxoglutarate dehydrogenase activity in homogenates of cultured skin fibroblasts was reduced to about 25% of control values in both children. Although the pathogenetic mechanisms leading to brain damage remain obscure, the finding strongly suggest an autosomal recessive neurometabolic disease with predominant involvement of the extrapyramidal system.

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“…Mildly increased urinary levels of 2-HG were detected in patients affected with multiple acyl-CoA dehydrogenase deficiency (Goodman et al 1980;Przyrembel et al 1976), pyruvate decarboxylase deficiency (E1) (Chalmers et al 1977), and dihydrolipoyl dehydrogenase (Kuhara et al 1983), and in a disorder of gluconeogenesis, pyruvate carboxylase deficiency (Van Biervliet et al 1977). In 1980, a patient was reported who excreted 2-HG to a much greater extent than patients with one of the disorders described above (Chalmers et al 1980).…”

mentioning

confidence: 93%

D‐2‐Hydroxyglutaric aciduria: Unravelling the biochemical pathway and the genetic defect

Struys

2006

J of Inher Metab Disea

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D-2-Hydroxyglutaric aciduria (D-2-HGA) is a neurometabolic inherited disorder first described in 1980. In the following years, it became clear that the clinical phenotype of the disease varies widely from severe neonatal to asymptomatic. However, the sparse biochemical knowledge made D-2-HGA a poorly understood disease. Much progress has been made in the last five years in various studies, revealing two human enzymes that play a role in the metabolism of D-2-hydroxyglutarate (D-2-HG): hydroxyacid-oxoacid transhydrogenase (HOT) and D-2-HG dehydrogenase. HOT is expected to be responsible for the formation of D-2-HG, while D-2-HG dehydrogenase converts D-2-HG into 2-ketoglutarate. We demonstrated pathogenic mutations in the D2HGD gene in patients with D-2-HGA, helping to unravel the primary defect causing D-2-HGA. However, in approximately 50% of the patients with D-2-HGA examined, no pathogenic mutations have yet been found.

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Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency

Cited by 24 publications

References 13 publications

Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis

Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis

A familial progressive neurodegenerative disease with 2-oxoglutaric aciduria

D‐2‐Hydroxyglutaric aciduria: Unravelling the biochemical pathway and the genetic defect

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